The yeast mitochondrial carrier proteins Mrs3p/Mrs4p mediate iron transport across the inner mitochondrial membrane

Elisabeth M Froschauer1, Rudolf J Schweyen, Gerlinde Wiesenberger

  • 1Max F. Perutz Laboratories, Department of Genetics, University of Vienna, Dr. Bohrgasse 9, A-1030 Vienna, Austria.

Insights

Yeast proteins Mrs3p and Mrs4p directly transport iron(II) across the inner mitochondrial membrane. This process is crucial for mitochondrial iron homeostasis, especially under iron-limiting conditions.

Area of Science:

  • Mitochondrial biology
  • Molecular transport
  • Cellular iron homeostasis

Background:

  • Yeast proteins Mrs3p and Mrs4p are mitochondrial carrier family members linked to iron homeostasis.
  • A vertebrate homolog, mitoferrin, is vital for iron utilization in red blood cells and acts as a mitochondrial iron importer.
  • Previous studies suggested Mrs3/4 proteins facilitate mitochondrial iron transport under limited iron conditions.

Purpose of the Study:

  • To directly investigate the role of Mrs3p and Mrs4p in mitochondrial iron(II) uptake.
  • To characterize the transport mechanism and substrate specificity of Mrs3/4p.

Main Methods:

  • Utilized isolated yeast inner mitochondrial membrane vesicles (SMPs).
  • Employed the iron-sensitive fluorophore PhenGreen SK (PGSK) to measure iron(II) uptake.
  • Compared iron(II) transport in wild-type, mrs3/4 deletion mutant, and Mrs3/4p overproducing strains.

Main Results:

  • Wild-type SMPs demonstrated rapid Fe(2+) uptake, dependent on external Fe(2+) concentration and stimulated by acidic pH.
  • SMPs lacking Mrs3/4 (mrs3/4Δ) showed significantly reduced Fe(2+) uptake.
  • Overproduction of Mrs3/4p led to increased Fe(2+) uptake rates.
  • Mrs3/4p transported Cu(2+) but not Zn(2+) or Cd(2+).

Conclusions:

  • The yeast carrier proteins Mrs3p and Mrs4p directly transport Fe(2+) across the inner mitochondrial membrane.
  • Mrs3/4p-mediated iron transport is dependent on the pH gradient and is enhanced during iron scarcity.
  • These findings confirm Mrs3/4p as essential mitochondrial iron transporters.

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